We have isolated and sequenced a large family of 20 novel endogenous neuropeptides in the nematode, Ascaris suum. Preliminary experiments have shown that each of the peptides tested so far has potent activity on the neuromuscular system of Ascaris. Some causes paralysis, others exaggerate locomotory movements. Different peptides affect the physiological properties of different neurons in the motornervous system in a variety of ways. The peptides fall into at least 4 subfamilies based on their amino acid sequences. We have shown that one of these subfamilies, comprising 6 peptides, is derived from a precursor protein encoded by a single mRNA coding sequence, strongly reinforcing the concept of subfamilies. Our long-term aim is to understand the role of these peptides in the control of locomotion in Ascaris. In this proposal we plan to use electrophysiological techniques to characterize the signalling pathways mediated by each peptide, and to use molecular biological techniques to determine the genetic organization of this family of peptides. Our hypothesis is that there is a direct correspondence between the subfamilies of peptides defined three ways: by amino acid sequence, by physiological action, and by co-expression on a transcript. We predict that subfamilies exist because each subfamily is the product of a distinct transcript that organizes the co-expression of peptides having similar biological activity.